Real-World Data on Tezepelumab in Patients With Severe Asthma in Germany.

BACKGROUND: Tezepelumab is a novel biologic blocking thymic stromal lymphopoetin, approved for severe asthma irrespective of biomarker levels or phenotype. OBJECTIVE: To characterize a real-world tezepelumab patient cohort and the efficacy among various asthma phenotypes. METHODS: We performed a retrospective, multicenter study on patients with severe asthma initiating tezepelumab. Clinical response was evaluated at 3 and 6 months. RESULTS: We included 129 patients with an average age of 52.5 ± 13.1 years, 59.7% were female. The majority (86.0%) had increased type 2 (T2) biomarkers, 68.2% an allergic and 31.8% an eosinophilic phenotype. 23.3% of patients were biologic-naive. 22 (18.2%) patients discontinued tezepelumab therapy owing to suspected side effects or insufficient efficacy. At 6 months' follow-up, median reduction in annualized exacerbation rate was-1 [25th percentile; 75% percentile {-2.9; 0.0}], the reduction of oral corticosteroid dose among patients with long-term oral corticosteroid therapy was -5 mg [-10; 0] and the Asthma Control Test (ACT) improved by 2 [0; 5] points. A treatment response according to Biologic Asthma Response Score of 80.8% was demonstrated. There were no significant differences in treatment response between T2-high versus T2-low, early- versus adult-onset and eosinophilic versus non-eosinophilic asthma. Prior treatment with other biologics was associated with inferior treatment response. CONCLUSIONS: In this real-life cohort, including a large proportion of patients with history of previous biologic use and encompassing various subgroups, the majority responded to tezepelumab. Our data further suggest a steroid-sparing effect of tezepelumab.

Impact of interstitial lung disease on left ventricular myocardial function.

BACKGROUND: Interstitial lung disease (ILD) comprises a wide variety of pulmonary parenchymal disorders within which progressive fibrosing ILD (PF-ILD) constitutes a phenotypic subset. By use of speckle tracking-based strain analysis we aimed to evaluate the degree of left ventricular (LV) dysfunction in progressive vs. non-progressive fibrosing ILD (non-PF-ILD). METHODS: A total of 99 ILD patients (mean age 63.7 ± 13.5 years, 37.4% female), composed of 50 PF-ILD and 49 non-PF-ILD patients, and 33 controls were prospectively enrolled and underwent conventional and speckle tracking echocardiography. Additional laboratory and pulmonary function testing, as well as six-minute walk test were performed. RESULTS: As compared to the non-PF-ILD cohort, PF-ILD patients exhibited a significantly impaired forced vital capacity (2.4 ± 1.0l vs. 3.1 ± 0.9l, p = 0.002), diffusion capacity for carbon monoxide (DLCO, 25.6 ± 16.3% predicted vs. 43.6 ± 16.67% predicted, p <0.001) and exercise capacity response as measured by the six-minute walk test distance (268.1 ± 178.2m vs. 432.6 ± 94.2m, p <0.001). Contrary to conventional echocardiographic LV parameters, both regional and global longitudinal LV strain measurements were significantly altered in ILD patients as compared to controls. No differences in LV strain were found between both patient groups. Significant correlations were observed between global longitudinal strain, on the one hand, and systemic inflammation markers, total lung capacity (TLC) and DLCO, on the other hand (high-sensitivity C-reactive protein: Pearson´s r = -0.30, p< 0.001; interleukin-6: Pearson´s r = -0.26, p = 0.007; TLC % predicted: Pearson´s r = 0.22, p = 0.02; DLCO % predicted: Pearson´s r = 0.21, p = 0.02). CONCLUSIONS: ILD is accompanied by LV dysfunction. LV functionality inversely correlates with the severity of the restrictive ventilatory defect and inflammation marker levels. These observations support the assumption of persistent low-grade systemic inflammation that may link systemic cardiovascular function to ILD status.

High prevalence of peripheral and carotid artery disease in patients with interstitial lung diseases.

Background: Interstitial lung diseases (ILD) are a heterogenous group of diseases, which have pulmonary fibrosis, restrictive lung disease, and decreased diffusion capacity as a common final path. Premature death frequently results not from ILD itself but from comorbidities. Peripheral artery disease (PAD) is a common comorbid disease in different chronic lung diseases. The focus of the present study is to clarify the prevalence of PAD in ILD. Patients and methods: A total of 97 patients with ILD and 30 controls were included in the study. Patients with ILD were subdivided into two groups according to the progression of pulmonary fibrosis: progressive fibrosing and non-progressive fibrosing ILD (PF-ILD and nPF-ILD, respectively). All participants underwent standard angiological and pneumological diagnostic procedures including six-minute walking test, measurement of ankle-brachial-index, and colour-coded duplex sonography. Results: We observed no relevant differences in the baseline characteristics except age. Both, PF-ILD and nPF-ILD patients, presented with a highly increased incidence of atherosclerotic lesions compared to the control group (p<0.001). PAD was present in all patients with PF-ILD and in 73% of patients with nPF-ILD. These results were confirmed by age-adjusted regression analyses. Conclusions: The present results indicate that ILD is an independent risk factor for atherosclerosis. Patients with PF-ILD are more severely affected than nPF-ILD patients with age as a confounding variable. Atherogenesis in ILD may be mediated by increased cardiovascular risk, systemic inflammation and chronic hypoxemia.

Prevalence of sleep-disordered breathing in patients with mitral regurgitation and the effect of mitral valve repair.

PURPOSE: The relationship between chronic heart failure and sleep-disordered breathing (SDB) has been frequently described. However, little is known about the association of mitral regurgitation (MR) and SDB or the impact of transcatheter mitral valve repair (TMVR) on SDB. Our aims were first to determine the prevalence of SDB in patients with MR, and second to determine the effect of TMVR on SDB. METHODS: Patients with MR being evaluated for TMVR at the University Hospital Bonn underwent polygraphy (PG) to determine the prevalence of SDB. After TMVR, a subset of patients was followed up with transthoracic echocardiography (TTE) and PG to evaluate the effect of TMVR on SDB. RESULTS: In 53 patients, mean age was 76.0 ± 8.5 years and 62% were male. Patients predominantly had more than moderate mitral regurgitation (94%). SDB was highly prevalent (68%) with predominantly central sleep apnoea (CSA, 67%). After TMVR in 15 patients, the apnoea/hypopnoea index (AHI) and central apnoea index (AI) were significantly reduced among patients with SDB (AHI - 8.0/h, p = 0.021; central AI - 6.9/h, p = 0.046). The left atrial volume index (LAVI) at baseline was significantly higher in patients with CSA than in patients with obstructive sleep apnoea (OSA) and was significantly reduced after TMVR (63.5 ml/m2 ± 27.2 vs. 38.3 ml/m2 ± 13.0; - 18.4 ml/m2, p = 0.027). CONCLUSION: SDB, especially CSA, is highly prevalent in patients with mitral regurgitation. In the follow-up cohort TMVR led to a significant reduction of the AHI, predominantly of central events. The findings of the study suggest that TMVR may be a suitable therapy not only for MR but also for the accompanying CSA. LAVI may be a useful indicator for CSA in patients with MR.

Impact of short-term pausing of oral corticosteroids on blood eosinophil count in patients with severe asthma.

BACKGROUND: The peripheral blood eosinophil count (BEC) is a well-established and easily accessible biomarker for asthma patients and crucial for the therapeutic decision regarding monoclonal antibody (mAB) therapy. Oral corticosteroid therapy frequently hinders the correct evaluation of BEC in patients with severe asthma, but a discontinuation of such therapy frequently comes along with severe side effects. Therefore, we examined the effect of a short 24-hour pause of OCS treatment on BEC in patients with severe asthma and followed-up whether patients with a then increased eosinophil count benefited from mAB-therapy, as expected. METHODS: In this multicentre study we retrospectively included 24 patients with severe asthma and OCS therapy and determined their BEC count. Ten patients, where BEC count was obtained in the morning before taking medication (a de-facto 24-hour OCS pause), were assigned to group 1. Fourteen patients, where BEC was obtained after OCS tapering were assigned to group 2. Those who then received mAB treatment were followed up for treatment response (OCS dose, annual acute exacerbations, increase in forced expiratory volume in one second [FEV1] and asthma control test [ACT]) after ≥3 months. RESULTS: We included 24 patients with a median age of 60.5 [IQR: 17.3] years. Regarding all baseline characteristics except FEV1 (l), both groups did not differ significantly.Among all 24 patients, after pausing OCS therapy for 2 [5.5] days the BEC increased significantly from 125.0/µl [125] to 300/µl [232.5] (p<0.001). In both individual groups BEC increased significantly as well (150 [123] to 325 [305], p=0.005 and 70 [150] to 280 [255], p<0.001), with no significant difference for increase (BEC +170/µl [205.0] vs. +195 [222.5], p=0.886). Of all 24 patients, 13 (54.2%) reached eosinophil levels ≥300/µl, while 12 of them had not exceeded this threshold before.Subsequently, 20 patients (83.3%) received mAB-therapy with 55.5% demonstrating a good treatment response within 6 [1.5] months. The response rate in patients with BEC count ≥300/µl was even higher (75.0%). There was no difference in the treatment response rate between group 1 and 2 (p=0.092). CONCLUSION: After just a short 24-hour pause of OCS therapy it was possible to demask a relevant eosinophilia in asthma patients, without risking severe side effects. In this manner, we enabled the possibility of achieving successful targeted mAB-therapy, according to the patient's individual asthma phenotype.

Pulmonary affection of patients with Pseudoxanthoma elasticum: Long-term development and genotype-phenotype-correlation.

Pseudoxanthoma elasticum (PXE) is a rare, heritable disease caused by various, mainly recessively transmitted mutations in the ABCC6 gene. Due to calcification of soft connective tissue phenotypic hallmarks are progressive loss of vision, alternation of the skin and early onset atherosclerosis. Beside these main features patients also suffer from impaired alveolar diffusion. The present study focused on impaired lung functioning based on a large cohort of patients with PXE, its long-term development, and genotype-phenotype correlation. Retrospectively, 98 patients and 45 controls were enrolled. All patients underwent body plethysmography and carbon monoxide diffusion testing. Of 35 patients three or more body plethysmographic records were available for long-term analysis. For genotype-phenotype analysis ABCC6 genotypes were grouped as two missense, mixed, or two nonsense mutations. Patients with PXE showed significantly reduced vital capacity (p < 0.05), diffusion capacity (p < 0.01), and diffusion transfer coefficient (p < 0.05). Over a mean period of 38 months diffusion capacity (p < 0.05) and diffusion transfer coefficient (p < 0.01) dropped significantly whereas lung volumes remained unchanged. Genotype-phenotype correlation revealed no connection between gene variants and lung functioning. In conclusion, PXE is accompanied by progressive reduction of alveolar diffusion indicating progressive alterations of lung tissue. Genotype-phenotype correlation with genotypes sorted as missense and nonsense mutations do not explain impaired lung functioning.

Impact of prior smoking exposure and COPD comorbidity on treatment response to monoclonal antibodies in patients with severe asthma.

Patients suffering from severe asthma may benefit from an antibody treatment irrespective of their status as an ex-smoker https://bit.ly/3fYC8tC.

Endoscopic Lung Volume Reduction in COPD: The Impact of Coil Implantation on Patients' Physical Activity.

Endoscopic lung volume reduction (ELVR) is an emerging therapy option for the treatment of severe emphysema in COPD. To which extent patients profit from lung volume reduction via coils (LVRC) regarding morbidity, mortality, and quality of life is not clear yet. In this monocentric prospective cohort study, 13 COPD patients with severe emphysema (residual volume [RV] >225%) were enrolled at the University Hospital of Bonn. Activity measurements were assessed by a validated accelerometer wristband. By LVRC, RV could be reduced by 0.13 L to 5.54 ± 1.29 L. We could show a clinically relevant improvement in patients' physical activity after LVRC, measured as daily step count (497.7 ± 72.6 vs. 1,913.7 ± 182.7 steps/day, p = 0.03) and mean daily active energy expenditure (714.4 ± 73.6 vs. 2,321.3 ± 163.9 joules, p = 0.03). This improvement in physical activity is possibly associated with a positive effect on patients' morbidity and mortality.